Intramolecular Friedel‐Crafts Acylation of [11C]Isocyanates Enabling the Radiolabeling of [carbonyl‐11C]DPQ

Abstract α,β‐aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short‐lived (t 1/2 =20.3 min), β + ‐decaying carbon‐11, which has prevented their application as positron emission tomography tracers. Herein, we developed, optimized, and applied a widely applicable, one‐pot, quick, robust and automatable radiolabeling method for α,β‐aromatic lactams starting from [ 11 C]CO 2 using the reagent POCl 3 ⋅AlCl 3 . This method proceeds via intramolecular Friedel‐Crafts acylation of in situ formed [ 11 C]isocyanates and shows a broad substrate scope for the formation of five‐ and six‐membered rings. We implemented our developed labeling method for the radiosynthesis of the potential PARP1 PET tracer [ carbonyl ‐ 11 C]DPQ in a clinical radiotracer production facility following the standards of the European Pharmacopoeia.